study of imatinib mesylate in combination with hydroxyurea versus hydroxyurea alone as an oral therapy in patients with temozolomide resistant progressive glioblastoma

Conditions: Glioblastoma Multiforme; Astrocytoma

Summary: this is a phase iii study comparing imatinib mesylate and hydroxyurea combination therapy with hydroxyurea monotherapy in patients with temozolomide resistant progressive glioblastoma.


Eligibility criteria:
inclusion criteria: * signed informed consent prior to initiation of any study procedure. * patients \>= 18 years of age. * histological confirmed diagnosis of glioblastoma multiforme / astrocytoma world health organization (who) grade iv by a reference pathologist * eastern cooperative oncology group (ecog) performance status of 0, 1 or 2. * adequate hepatic, renal and bone marrow function as defined by the following: total bilirubin \ 1.5 x109/l, platelets \> 100 x109/l and hemoglobin \> 10 g/dl. * female patients of childbearing potential with a negative pregnancy test within 7 days of initiation of study drug dosing. postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. male and female patients of reproductive potential who agree to employ an effective barrier method of birth control throughout the study, and for up to 3 months following discontinuation of study drug. * life expectancy of \>3 months. * mri available every 6 weeks for disease management * no intercerebral inflammation * irradiation therapy 54 to 62 gy finished or less according to national standard * chemotherapy at least 1 temozolomide containing regimen finished, no established chemotherapy regiment available and progression under chemotherapy or in between 6 months following the last chemotherapy. * leucocytes \> 2.500/µl, to be controlled once a week * thrombocytes \> 80.000/µl, to be controlled once a week * ensured compliance * patients who had a second or third resection after disease progression cannot be included earlier than 2 weeks following the resection. mri should be performed not later than 72 h post operation. if patients are to be included later than 4 weeks after the resection, a new baseline mri must be performed. exclusion criteria: * female patients who are pregnant or breast-feeding. * patients who have been treated with any investigational agent(s) within 28 days of the first day of administration of study drug. * patients with uncontrolled medical disease such as diabetes mellitus, thyroid dysfunction, neuropsychiatric disorders, infection, angina or grade 3 or 4 cardiac problems as defined by the new york heart association criteria. * patients with other malignant disorders. * patient with acute or known chronic liver disease (i.e., chronic active hepatitis, cirrhosis). * patients who are known to be hiv positive (no specific tests are required for confirmation of eligibility). * expected incompliance according to treatment, treatment diary and examination schedule * not confirmed histological diagnosis glioblastoma multiforme/astrocytoma who grade iv * other drugs with potential cytostatic main or side effect * no or inadequate chemotherapy or irradiation therapy * patients without hematological recovery after previous chemotherapy who have been treated with chemotherapy within 28 days of the first day of administration of study drug. other protocol-specific inclusion /exclusion criteria may apply.

Keywords: open label imatinib mesylate hydroxyurea temozolomide resistant protein tyrosine kinases adenocarcinoma glioblastoma multiforme astrocytoma brain tumor brain cancer